Phosducin-like 3 is a novel prognostic and onco-immunological biomarker in glioma: A multi-omics analysis with experimental verification

Abstract

Malignant glioma is the most frequent primary tumor of the central nervous system. PDCL3 is a member of the phosducin-like protein family, and its imbalance has been shown to be associated with several human diseases. However, the underlying role of PDCL3 in human malignant cancers, especially in malignant gliomas, is unclear. In this study, we combined public database analysis and experimental verification to explore the differential expression, prognostic value and potential functions and mechanisms of PDCL3. The results revealed that PDCL3 is upregulated in multiple cancers and acts as a potential prognostic biomarker of glioma. Mechanistically, PDCL3 expression is associated with epigenetic modifications and genetic mutations. PDCL3 may directly interact with the chaperonin-containing TCP1 complex, regulating cell malignancy, cell communication and the extracellular matrix. More importantly, the association of PDCL3 with the infiltration of immune cells, immunomodulatory genes, immune checkpoints, cancer stemness and angiogenesis suggested that PDCL3 may regulate the glioma immune landscape. Furthermore, PDCL3 interference also decreased the proliferation, invasion and migration of glioma cells. In conclusion, PDCL3 is a novel oncogene and can be adopted as a biomarker with value in assisting clinical diagnosis, predicting patient outcomes and assessing the immune landscape of the tumor microenvironment in glioma.

Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship

“…Concerning methylation, however, DNASE1L3 was positively correlated the strongest with DNA stemness score in TGCT among all cancers [70]. Notably, in a different study, DNA stemness score was also positively correlated with the overexpression of a gene, namely PDLC3, and no correlation with overall survivor or progression-free survival was found [71]. In a study on the signal and transducer and activator of transcription (STAT) family, however, a negative correlation between DNA stemness score and STAT5A expression was found in TGCT, while this gene's overexpression was strongly associated with poor overall survival [72].…”

PDCL3 is a prognostic biomarker associated with immune infiltration in hepatocellular carcinoma

“…Further survival analysis indicated that patients with high PDCL3 expression in tumors and low macrophage infiltration had a poorer prognosis, partly attributed to reduced macrophage infiltration. Previous research on immune infiltration in glioblastomas suggested that M2-type macrophage infiltration influences glioblastoma patient prognosis through angiogenesis regulation, extracellular matrix remodeling, and glioblastoma cell invasiveness [ 35 ]. Therefore, we hypothesize that high PDCL3 expression in LIHC affects the biological behavior of tumors by reducing macrophage infiltration.…”

PDCL3 is a Novel Oncogenic Indicator in Hepatocellular Carcinoma using Comprehensive Bioinformatics Analysis and in vitro Validation

“…Moreover, PDCL3 is found to play an important role in apoptosis, possibly because PDCL3 adjuvants the folding of one or more pro-apoptotic factors 10 . Other studies have illustrated that differential expression or mutations in PDCL3 are associated with the development and progression of malignant gliomas 11 , fetal megacystis-microcolon 12 , and Alzheimer's disease 13 . Thus, PDCL3 is a key protein involved in tumor progression, however, its role in the pathogenesis of HCC has not been previously investigated.…”